2. Academic Validation
  3. KIF22 promotes multiple myeloma progression by regulating the CDC25C/CDK1/cyclinB1 pathway

KIF22 promotes multiple myeloma progression by regulating the CDC25C/CDK1/cyclinB1 pathway

  • J Cancer Res Clin Oncol. 2024 May 7;150(5):239. doi: 10.1007/s00432-024-05747-w.
Meng Zhai 1 2,  Jiyu Miao 1 2,  Ru Zhang 1 2,  Rui Liu 1 2,  Fangmei Li 1 2,  Ying Shen 1 2 3,  Ting Wang 1 2,  Xuezhu Xu 1 2,  Gongzhizi Gao 1 2,  Jinsong Hu 4,  Aili He 5 6 7 8,  Ju Bai 9 10
Affiliations

Affiliations

  • 1 Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 2 Xi'an Key Laboratory of Hematological Diseases, Xi'an, China.
  • 3 National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
  • 4 Department of Cell Biology and Genetics, Xi'an Jiaotong University Health Science Center, 76 Yanta West Road, Xi'anShaanxi, 710061, China.
  • 5 Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. heaili@xjtu.edu.cn.
  • 6 Xi'an Key Laboratory of Hematological Diseases, Xi'an, China. heaili@xjtu.edu.cn.
  • 7 National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. heaili@xjtu.edu.cn.
  • 8 Department of Tumor and Immunology in Precision Medical Institute, Xi'an Jiaotong University, Xi'an, China. heaili@xjtu.edu.cn.
  • 9 Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. 13720542359@163.com.
  • 10 Xi'an Key Laboratory of Hematological Diseases, Xi'an, China. 13720542359@163.com.
PMID: 38713252 DOI: 10.1007/s00432-024-05747-w
Abstract

Purpose: Multiple myeloma (MM) is an incurable hematological malignancy characterized by clonal proliferation of malignant plasma B cells in bone marrow, and its pathogenesis remains unknown. The aim of this study was to determine the role of Kinesin family member 22 (KIF22) in MM and elucidate its molecular mechanism.

Methods: The expression of KIF22 was detected in MM patients based upon the public datasets and clinical samples. Then, in vitro assays were performed to investigate the biological function of KIF22 in MM cell lines, and subcutaneous xenograft models in nude mice were conducted in vivo. Chromatin immunoprecipitation (ChIP) and luciferase reporter assay were used to determine the mechanism of KIF22-mediated regulation.

Results: The results demonstrated that the expression of KIF22 in MM patients was associated with several clinical features, including gender (P = 0.016), LDH (P < 0.001), β2-MG (P = 0.003), percentage of tumor cells (BM) (P = 0.002) and poor prognosis (P < 0.0001). Furthermore, changing the expression of KIF22 mainly influenced the cell proliferation in vitro and tumor growth in vivo, and caused G2/M phase cell cycle dysfunction. Mechanically, KIF22 directly transcriptionally regulated cell division cycle 25C (CDC25C) by binding its promoter and indirectly influenced CDC25C expression by regulating the ERK pathway. KIF22 also regulated CDC25C/CDK1/cyclinB1 pathway.

Conclusion: KIF22 could promote cell proliferation and cell cycle progression by transcriptionally regulating CDC25C and its downstream CDC25C/CDK1/cyclinB1 pathway to facilitate MM progression, which might be a potential therapeutic target in MM.

Keywords

CDC25C; Cell cycle; KIF22; Multiple myeloma; Proliferation.

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